Late Reduction of Cocaine Cravings in a Randomized, Double-Blind Trial of Aripiprazole vs Perphenazine in Schizophrenia and Comorbid Cocaine Dependence
Late Reduction of Cocaine Cravings in a Randomized, Double-Blind Trial of Aripiprazole vs Perphenazine in Schizophrenia and Comorbid Cocaine Dependence
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DOI：
10.1097/jcp.0000000000000789
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发表时间：
2017-12-01
影响因子：
2.9
通讯作者：
Ronan, Patrick J.
中科院分区：
文献类型：
--
作者：
Beresford, Thomas;Buchanan, Jennifer;Ronan, Patrick J.
目的精神分裂症谱系障碍和国际疾病统计分类第10次修订版可卡因依赖共同存在，这两种疾病都引起了大脑中多巴胺的传递效应，是一种特别具有破坏性的疾病，通常难以治疗。传统的精神抑制剂阻断多巴胺受体，而阿立哌唑作为激动剂/拮抗剂调节多巴胺活性。我们测试多巴胺调制是否是上级多巴胺阻断在双diagnosispatients.Methods在一个随机的，双盲的，比较设计，可卡因依赖性精神分裂症患者积极使用可卡因接受阿立哌唑或奋乃静在8周的试验。主要结果针对无可卡因的尿液样本比例，而可卡因渴望分数是一个次要variable.Results受试者（N = 44）随机（n = 22每组）在基线没有差异。无可卡因尿样的比例在药物组之间没有差异。对比第3至5周与第6至8周，发现阿立哌唑的渴望在晚期显著减少。在各分量表上，渴求强度分别下降了1.53 ± 0.43（P < 0.0005）分，渴望频率增加1.4 +/- 0.40（P > 0.0004）分，渴求持续时间增加1.76 ± 0.44结论阿立哌唑对渴求项目的药物效应平均在治疗第6周出现，在药物暴露时间之前未见。数据表明，多巴胺调节减少可卡因的渴望，但需要一个适应期。为了更好地了解作用机制，阿立哌唑的试验可能是有用的。在临床上，渴望的减少可能为正在进行的行为治疗提供更清晰的焦点。它还可以针对复发的严重程度提供更长期的治疗效果。
Purpose Co-occurring schizophrenia spectrum disorder and International Statistical Classification of Diseases, 10th Revision cocaine dependence present a particularly destructive constellation that is often difficult to treat. Both conditions raise dopamine transmission effects in the brain. Traditional neuroleptics block dopamine receptors, whereas aripiprazole modulates dopamine activity as an agonist/antagonist. We tested whether dopamine modulation is superior to dopamine blocking in dual-diagnosis patients.Methods In a randomized, double-blind, comparison design, cocaine-dependent schizophrenic subjects actively using cocaine received either aripiprazole or perphenazine in an 8-week trial. Primary outcome targeted cocaine-free urine sample proportions, whereas cocaine craving scores were a secondary variable.Results Subjects (N = 44) randomized (n = 22 per group) did not differ at baseline. The proportion of cocaine-free urine samples did not differ by medication group. Contrasting weeks 3 to 5 vs 6 to 8 revealed significant late reductions in craving with aripiprazole. On the respective 5-point subscales, craving intensity decreased by 1.53 0.43 (P < 0.0005) points, craving frequency by 1.4 +/- 0.40 (P > 0.0004) points, and craving duration by 1.76 +/- 0.44 (P > 0.0001) points.Conclusions A drug effect of aripiprazole on craving items appeared at week 6 of treatment, on average, and was not seen before that length of drug exposure. The data suggest that dopamine modulation reduces cocaine cravings but requires an acclimation period. To understand the mechanism of action better, a trial of depot aripiprazole may be useful. Clinically, a reduction in craving potentially offers a clearer focus for ongoing behavioral treatment. It may also offer a longer-term treatment effect with respect to the severity of relapse.